International FOP Association on Overcoming Clinical Trial Challenges in One-in-a-Million Disease

FOP is widely recognized as the only known disease in which one tissue system effectively transforms into another. In affected individuals, skeletal muscle and connective tissues gradually undergo a process known as heterotopic ossification, resulting in the formation of bone outside the normal skeleton.

While certain muscles, including the diaphragm, tongue, heart muscle and retinal muscles, are typically spared, most other muscle tissue can be affected. As new bone develops, patients can become progressively immobilized as abnormal skeletal structures form.

Describing this process, Davis explained that “the muscle turns over into bone, which basically means that these patients become encased in a second skeleton.” This abnormal ossification can significantly restrict chest expansion, often leading to severe respiratory and cardiac complications due to reduced space for lung and heart function.

From a genetic standpoint, FOP is driven by a single point mutation, with approximately 97% of patients sharing the same genetic defect. The gene responsible for the condition was identified roughly two decades ago, enabling clearer diagnostic pathways. However, despite improved diagnostic certainty, the disease’s unique pathophysiology continues to pose substantial therapeutic challenges.

Founded in 1988, the IFOPA initially operated as a peer-support network connecting individuals and families affected by the condition. In the early years, Davis explained that patients were often focused on practical day-to-day concerns, asking one another questions such as, “What do you eat? Do you have a paid caregiver? Do you have a career?” In an era before widespread digital communication, patients and caregivers exchanged letters and made long-distance phone calls to share practical guidance on navigating daily life with FOP.

Early community efforts soon expanded to include fundraising for research, helping transform IFOPA into an organization that both supports patients and actively advances scientific discovery. Although originally established in the United States, the association quickly developed international connections, laying the groundwork for its current global reach.

A significant milestone came in 2007 with the creation of the International Presidents’ Council, which connects leaders from independent FOP organizations worldwide. This platform facilitates collaboration on research funding and clinical trials, knowledge sharing and coordination of family support initiatives across countries. Today, IFOPA’s programs are accessible globally, with translation support enabling participation regardless of geographic location.

Among these initiatives is the L.I.F.E Awards program (Living Independently with Full Equality), which provides stipends for adaptive equipment, home modifications, educational opportunities and other resources aimed at improving quality of life. In a recent funding cycle, more than half of award recipients were based outside the United States, highlighting the association’s international impact.

As research momentum has increased, IFOPA has played a central role in supporting clinical trial development. FOP’s ultra-rare status presents significant operational challenges, particularly in patient recruitment.

For many years, prevalence estimates suggested the disease affected approximately one in two million individuals. However, a 2021 IFOPA-led study refined that estimate to one in one million, improving feasibility assessments for drug developers. Even so, with an estimated global diagnosed population of around 1,000 individuals across all age groups and regions, trial enrollment demands can represent a substantial proportion of the total patient community.

Davis noted that at one point, five active clinical trials collectively required participation from roughly one-third of the world’s diagnosed population, creating logistical and eligibility constraints. Despite these hurdles, the FOP community successfully met enrollment targets, reflecting both strong patient engagement and coordinated global outreach.

The discovery of the FOP-causing gene in 2006 marked a turning point for the field. Researchers in the United States and the United Kingdom identified multi-generational families affected by the condition, enabling genetic analysis that pinpointed the mutation responsible. Since then, Davis has described research activity as “like this tsunami — like a good tsunami, a good wave — of research and drug development activity.”

IFOPA has also fostered collaboration between researchers studying genetic FOP and those investigating non-genetic heterotopic ossification, which can occur following trauma. By sharing insights into mechanisms of abnormal bone formation, these partnerships aim to advance understanding and therapeutic development across both patient groups.

To further support therapeutic innovation, IFOPA launched the FOP Drug Development Forum in 2014, a meeting designed to bring together academic researchers, clinician-scientists and pharmaceutical companies with a singular focus on advancing treatments for FOP.

The forum provides a structured environment for reviewing approved therapies, discussing lessons from ongoing clinical trials and exploring emerging drug targets. It also offers a space for sharing unpublished findings, which can accelerate collective learning across the research ecosystem.

A distinguishing feature of the event is the inclusion of patient advisory sessions. Davis noted that many researchers attending the meeting have “only seen FOP in a mouse or some other cellular model,” and direct interaction with patients can reshape how scientific priorities are defined. Such engagement can influence endpoint selection, pain management research and broader therapeutic strategy.

The upcoming 2026 FOP Drug Development Forum in Toronto is expected to coincide with key regulatory milestones, including the potential FDA decision on a second investigational therapy currently under review.

Looking ahead, IFOPA’s priorities are closely aligned with the evolving therapeutic landscape. One central focus is supporting regulatory review processes and ensuring global access to newly approved treatments. To strengthen patient input into these decisions, the organization is pursuing an externally led patient-focused drug development meeting with the FDA, which would culminate in a comprehensive “Voice of the Patient” report.

Such evidence can inform not only regulatory evaluations but also reimbursement discussions with public and private payers, helping ensure that clinical trial outcomes translate into real-world treatment availability.

Another major priority is the continued expansion of IFOPA’s patient registry, established in 2015 as the world’s only registry dedicated to FOP. Enhancements planned for the coming year include new tools and functionalities aimed at strengthening patient-owned data resources that support both research and care planning.

From a scientific perspective, Davis highlighted emerging questions about how approved therapies could reshape long-term disease management. She emphasized the importance of exploring future functional gains, asking whether clinicians might one day be able to “give patients a drug and then do surgery to remove a piece of extra bone.”

As drug development activity intensifies and global collaboration deepens, the FOP field appears to be entering a key phase. For IFOPA, the next stage involves ensuring that scientific breakthroughs translate into meaningful patient outcomes — from regulatory approvals and equitable access to innovative approaches that address long-standing functional limitations.

In one of the rarest genetic diseases known, sustained coordination among researchers, clinicians, sponsors and patient communities will be essential. Through its expanding global network and strategic focus on patient-centered evidence generation, the IFOPA continues to play a critical role in shaping the future of FOP research, clinical development and care.